chr1-108650351-C-T

Position:

• chr1-108650351-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001102592.2(HENMT1):​c.616G>A​(p.Glu206Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HENMT1 NM_001102592.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01

Genes affected

HENMT1 (HGNC:26400): (HEN methyltransferase 1) Enables small RNA 2'-O-methyltransferase. Involved in RNA methylation. Predicted to be located in P granule. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41207248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HENMT1	NM_001102592.2	c.616G>A	p.Glu206Lys	missense_variant	7/8	ENST00000651461.1
HENMT1	NM_144584.3	c.616G>A	p.Glu206Lys	missense_variant	7/8
HENMT1	XM_005270411.2	c.640G>A	p.Glu214Lys	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HENMT1	ENST00000651461.1	c.616G>A	p.Glu206Lys	missense_variant	7/8		NM_001102592.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	0.0094	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;.;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D;D;.;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Uncertain	0.044	D;D;D;T
Polyphen		1.0	D;.;D;.
Vest4		0.66
MutPred		0.43		Gain of methylation at E206 (P = 0.0029);Gain of methylation at E206 (P = 0.0029);Gain of methylation at E206 (P = 0.0029);Gain of methylation at E206 (P = 0.0029);
MVP		0.28
MPC		0.26
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.57
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-109192973; COSMIC: COSV100898677;